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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

A chemotherapy-free induction regimen for mantle-cell lymphoma (MCL) led to complete responses in three fourths of patients and partial responses in the remaining patients, with a favorable adverse event profile, in a small clinical trial.

Note that standard front-line care for MCL consists of intensive induction chemotherapy, which confers substantial toxicity and risk of second malignancies.

SAN DIEGO -- A chemotherapy-free induction regimen for mantle-cell lymphoma (MCL) led to objective responses in 100% of patients, associated with a favorable adverse event profile, results of a small clinical trial showed.

Three-fourths of patients achieved complete responses to induction therapy consisting of ibrutinib (Imbruvica) and rituximab (Rituxan), and the remaining patients had partial responses with the induction therapy. The 100% response rate remained consistent in analyses that incorporated biomarkers, prognostic index, and development of rash.

Many of the 50 patients enrolled in the trial had rapid and dramatic reductions in tumor burden, Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, reported here at the American Society of Hematology meeting.

"This chemotherapy-free regimen achieved an unprecedented 100% efficacy as frontline treatment for patients with newly diagnosed mantle-cell lymphoma," said Wang. "The complete response rate is high and still improving. This may provide a window of opportunity to reduce the use of frontline chemotherapy with improved efficacy and reduced toxicity."

Results with the chemotherapy-free induction regimen are promising but too preliminary to begin discussions about how they might influence clinical practice, said Elizabeth Budde, MD, PhD, of City of Hope in Duarte, Calif.

"The current trend in mantle cell lymphoma is toward less intense treatment and use of nonchemotherapy alternatives," Budde told MedPage Today. "Another small study reported last year, using lenalidomide [Revlimid] and rituximab, showed an overall response rate of 92% and complete responses in the 60s, fairly similar to what Dr. Wang reported with ibrutinib and rituximab.

"What both of the studies show is that nonchemotherapy-based upfront treatment has the potential to get good responses. One question about this approach is how long will the responses last. Another question is whether this kind of therapy can lead to minimal residual disease-free status. That would mean a potential cure."

Intense chemoimmunotherapy represents standard frontline care for MCL. The regimen commonly consists of eight cycles of rituximab (Rituxan) and hyper-CVAD chemotherapy, alternating with the combination of rituximab, methotrexate, and cytarabine. Two contemporary studies showed overall survival of 12.7 and 13.4 years with such regimens.

Intensive induction therapy also confers substantial toxicity and risk of second malignancies. One of the two recent studies showed a 9.4% incidence of second solid tumors and 3.1% incidence of myelodysplastic syndrome (MDS) and leukemia. The other showed a 6.2% incidence of MDS and leukemia. Because of the associated risks, the regimens should be limited to specialized centers, said Wang.

Effective frontline therapy for MCL affords the best opportunity to achieve a cure, as untreated MCL cells are in their most vulnerable, said Wang. The ideal frontline therapy would kill all MCL cells in a "first strike," eliminate any chance of secondary resistance, and achieve long-term remission. Optimized front-line therapy could become a shortcut to an MCL cure.

In the setting of relapsed/refractory MCL, ibrutinib monotherapy achieved an objective response rate of 68%. The ibrutinib-rituximab combination led to objective responses in almost 90% of patients.

Using the two agents in tandem might leverage a "compartmental shift phenomenon" in MCL. Ibrutinib induces a transient increase in circulating MCL cells during initial tumor reduction. Wang and colleagues hypothesized that MCL cells drive into peripheral circulation would be more vulnerable to intravenous rituximab.

The clinical experience gave rise to the concept of a "window of opportunity" to use chemotherapy-free induction, followed by a reduced number of cycles of consolidation chemoimmunotherapy for young, fit patients with newly diagnosed, untreated MCL.

To evaluate window-of-opportunity principle, investigators enrolled 50 patients younger than 65 with newly diagnosed MCL. Treatment occurred in two phases. Patients received ibrutinib-rituximab induction and continued treatment for as long as 12 months to reach best response. If patients achieved a complete response at any time during the first phase, they entered the second treatment phase, consisting of four cycles of chemoimmunotherapy consolidation.

The 50 patients had a median age of 55, all had ECOG performance status of 0 or 1, and 72% had low-risk disease by MIPI criteria. All but seven patients had stage III/IV disease.

Wang presented data for 45 patients, 33 of whom completed both phases of treatment. He said 16 patients remained in the first phase of treatment and one in the second phase.

The chemotherapy-free induction led to complete responses in 73% of patients and partial responses in 27%. Response rates were consistent irrespective of baseline Ki-67 proliferation index, MIPI risk status, or severity of treatment-associated rash (a marker of response).

Wang showed several paired images of patients, showing dramatic reductions in tumor burden after as few as two cycles of therapy.

The median duration of response, progression-free survival, and overall survival had yet to be reached after a median follow-up of 9 months. No patient died or developed progressive disease.

The chemotherapy-free regimen was associated with minimal hematologic and mostly grade 1/2 nonhematologic toxicity. The most common nonhematologic adverse events were fatigue, myalgia, diarrhea, dizziness, rash, and skin disorders.

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